Acute herpes simplex virus (HSV) infection of the eye in humans frequently proceeds to a latent state. Recurrence of HSV involving the corneal stroma layers presents a difficult clinical problem for the ophthalmologist to control. Ocular HSV is the most serious and prevalent infectious cause of corneal blindness in the United States. The overall objective of this proposal is to elucidate 1) the mechanisms of acute, latent and recurrent HSV-induced ocular disease, and 2) virus-related factors which may be responsible for the more severe forms of herpetic disease. Several HSV strains with predictable ocular pathogenicity patterns will be compared following multiple in vitro passages in either corneal epithelium, stromal keratocytes or endothelium cell cultures. The virus-eye related properties to be studied include 1) virus adaptation to corneal derived cell cultures, 2) basis for stromal tropism and cell death, and 3) virus affinity for specific corneal cells.